Download Loss of function of C9orf72 causes motor deficits in a zebrafish

Loss of function of C9orf72 causes motor deficits in a zebrafish model of ALS
ALS and FTLD are prevalent neurodegenerative disorders which share common
clinical, pathological and genetic characteristics. Amyotrophic Lateral Sclerosis (ALS)
is the most common motor neuron disease characterized by progressive paralysis
caused by the gradual loss of upper and lower motor neurons. Frontotemporal Lobar
Degeneration (FTLD) is the second most common form of degenerative dementia,
affecting individuals younger than 65 years. FTLD comprises the progressive
atrophy of the frontal and temporal lobes of the brain and is distinguished by
deteriorations in language, behavior control and emotional management. While
traditionally considered as two separate etiologies, emerging clinical commonalities
between ALS and FTLD brought forth the concept of an ALS/FTLD disorder. The
ALS/FTLD link was finally consolidated with the recent discovery of C9orf72 gene,
as the most common genetic cause for both ALS and FTLDand encoding for a protein of unknown
function..
Here we report reduced levels of C9ORF72 gene expression in a French cohort of
ALS/FTLD patients. Interestingly, we also determined lowered C9orf72 transcript levels in
samples from sporadic cases of FTDand ALS/FTLD. Using the zebrafish
as a vertebrate genetic model, we investigated whether a decrease in C9orf72 levels
is sufficient to induce neuropathological processes. We show that blocking the
translation of C9orf72 results in specific locomotor deficits and axonopathy of the motor
neurons suggesting that C9orf72 could play an essential role in the functioning and viability of
these neurons and could represent a converging pathological mechanism in the ALS/FTLD
spectrum of neurodegenerative disease.
Publication reference
S. Ciura et al., 2013, Loss of function of C9orf72 causes motor deficits in a zebrafish model of ALS,
Annals of Neurology doi: 10.1002/ana.23946